Adult stem cells are the basic building blocks for wound repair and regeneration. Understanding how to stimulate their growth and development is critical to advancing regenerative medicine. Our laboratory studies adult stem cells in the hair follicle because they are accessible and divide at specific developmental ages. Recently, activating mutations in the RAS signaling pathway have been found in children with Costello and cardiofaciocutaneous (CFC) syndromes. These syndromes are associated with multiple skin defects that appear to affect the proliferation and differentiation of skin stem cells. We have recently developed several mouse models, which develop many of the same skin abnormalities as Costello and CFC patients, including excess skin production and hair loss. We propose to use our mouse models to 1) investigate the basis of RAS- induced hair cycle defects, 2) determine the effect of RAS on adult stem cell proliferation, and 3) identify the downstream pathways that cause these defects. By understanding the function of RAS signaling in adult stem cells of the skin, new therapies could be developed to improve organ regeneration and wound repair. PUBLIC HEALTH RELEVANCE: Adult stem cells are the basic building blocks for wound repair and regeneration. We are studying the role of RAS in regulating adult stem cell proliferation and differentiation. As an experimental model, we will study how RAS affects adult stem cells of the hair follicle during regeneration and wound repair.